Pretreatment Serum Levels of IL-1 Receptor Antagonist and IL-4 Are Predictors of Overall Survival in Multiple Myeloma Patients Treated with Bortezomib

Multiple myeloma (MM) is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow with an elevation in monoclonal paraprotein, renal impairment, hypercalcemia, lytic bony lesions, and anemia. Immune cells and associated cytokines play a significant role in MM growth, progression, and dissemination. While some cytokines and their clinical significance are well described in MM biology, others remain relatively unknown. The present study examines the influence on progression-free survival (PFS) and overall survival (OS) by the serum levels of 27 selected cytokines in 61 newly diagnosed MM patients receiving first-line therapy with bortezomib-based regimens. The measurements were performed using a Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay and a MAGPIX Multiplex Reader, based on the Bio-Plex® 200 System (Bio-Rad). The following levels were determined: IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF. Most patients received a VCD chemotherapy regimen (bortezomib, cyclophosphamide, and dexamethasone). In the final multivariate model, IL-13 cytokine level (HR 0.1411, 95% CI: 0.0240–0.8291, p = 0.0302) and ASCT (HR 0.3722, 95% CI: 0.1826–0.7585, p = 0.0065) significantly impacted PFS. Furthermore, ASCT (HR 0.142, 95% CI: 0.046–0.438, p = 0.0007), presence of bone disease at diagnosis (HR 3.826, 95% CI: 1.471–9.949, p = 0.0059), and two cytokine levels—IL-1Ra (HR 1.017, 95% CI: 1.004–1.030, p = 0.0091) and IL-4 (HR 0.161, 95% CI: 0.037–0.698, p = 0.0147)—were independent predictors of OS. Three clusters of MM patients were identified with different cytokine profiles. In conclusion, serum pretreatment levels of IL-13 and IL-4 are predictors of better PFS and OS, respectively, whereas IL-1Ra pretreatment levels negatively impact OS in MM patients treated with bortezomib-based chemotherapy. Cytokine signature profile may have a potential influence on the outcome of patients treated with bortezomib.

Post-traumatic tension pneumocephalus and cystic angiomatosis of the skull: case report

Background Tension pneumocephalus is an increasing air trapped intracranially. Either spontaneous, post-traumatic or iatrogenic in origin. Cystic angiomatosis is a benign vascular hamartoma of the skeleton, when acquired it is either due to trauma or infection. This is the second report in English literature of post-traumatic delayed tension pneumocephalus with the development of cystic angiomatosis of the skull bone. Case presentation A 55-year-old gentlemen, presented with scalp swelling of 6-month duration with history of head trauma 2 years back. The swelling was increasing and associated with progressive walking difficulties and left hearing loss. CT scan and MRI revealed extradural pneumocephalus, parietal and occipital pneumatocele, and multiple lytic bony lesions, left mastoid hyperpneumatization with inner table defect communicating with the extradural space. Diagnosis of delayed extradural tension pneumocephalus was made. Surgical exploration revealed multiple bony defects of parietal, temporal and squamous part of left temporal bones, confirmed extradural pneumocephalus with intact dura. Repair of mastoid defect of (0.5 × 0.5 cm), excision of pneumatocele and removal of lytic bones were performed. Defective bone “cribriform-like” was identified at occipital and parietal regions centrally with a defect of nearly 7 × 7 cm. Future cranioplasty was considered after 6 months. Histology of bony chips and surrounding soft tissues is recognized as cystic angiomatosis. Conclusions The present case developed two very rare complications, following trivial head trauma; the first complication was delayed extradural tension pneumocephalus with pneumatocele which presented 2 years after trauma, the origin of air was from a defect of the inner table of the mastoid, the second complication was cystic angiomatosis of the skull bones. Both complications were managed surgically in one operative session as a combined neurosurgery and otolaryngology teams approach.

Craniofacial Osteomas: From Diagnosis to Therapy

An osteoma is a benign bone lesion with no clear pathogenesis, almost exclusive to the craniofacial area. Osteomas show very slow continuous growth, even in adulthood, unlike other bony lesions. Since these lesions are frequently asymptomatic, the diagnosis is usually made by plain radiography or by a computed tomography (CT) scan performed for other reasons. Rarely, the extensive growth could determine aesthetic or functional problems that vary according to different locations. Radiographically, osteomas appear as radiopaque lesions similar to bone cortex, and may determine bone expansion. Cone beam CT is the optimal imaging modality for assessing the relationship between osteomas and adjacent structures, and for surgical planning. The differential diagnosis includes several inflammatory and tumoral pathologies, but the typical craniofacial location may aid in the diagnosis. Due to the benign nature of osteomas, surgical treatment is limited to symptomatic lesions. Radical surgical resection is the gold standard therapy; it is based on a minimally invasive surgical approach with the aim of achieving an optimal cosmetic result. Reconstructive surgery for an osteoma is quite infrequent and reserved for patients with large central osteomas, such as big mandibular or maxillary lesions. In this regard, computer-assisted surgery guarantees better outcomes, providing the possibility of preoperative simulation of demolitive and reconstructive surgery.

Pretreatment Serum Levels of IL-1 Receptor Antagonist and IL-4 are Predictors of Overall Survival in Multiple Myeloma Patients Treated with Bortezomib

Multiple myeloma (MM) is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow with an elevation in monoclonal paraprotein, renal impairment, hypercalcemia, lytic bony lesions, and anemia. Immune cells and associated cytokines play a significant role in MM growth, progression, and dissemination. While some cytokines and their clinical significance are well described in MM biology, others remain relatively unknown. The aim of the present study was to assess the impact of pretreatment serum levels of 27 selected cytokines on progression-free survival (PFS) and overall survival (OS) in MM patients before first-line therapy with bortezomib-based regimens. Serum cytokine levels were assayed with a Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad) including IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF. A total of 61 MM patients were examined. Most patients received a bortezomib, cyclophosphamide and dexamethasone (VCD) chemotherapy regimen. In the final multivariate model, IL-13 cytokine level (HR 0.1411, 95% CI: 0.0240-0.8291, p = 0.0302), and ASCT (HR 0.3722, 95% CI: 0.1826-0.7585, p=0.0065) significantly impacted PFS. Furthermore, ASCT (HR 0.142, 95% CI: 0.046-0.438, p=0.0007), presence of bone disease at diagnosis (HR 3.826, 95% CI: 1.471-9.949, p=0.0059) and two cytokine levels- IL-1Ra (HR 1.017, 95% CI: 1.004-1.030, p= 0.0091) and IL-4 (HR 0.161, 95% CI: 0.037-0.698, p = 0.0147) were independent predictors of OS. Three clusters of MM patients were identified with different cytokine profiles. In conclusion, serum pretreatment levels of IL-13 and IL-4 are predictors of better PFS and OS, respectively, whereas IL-1Ra pretreatment levels negatively impact OS in MM patients treated with bortezomib-based chemotherapy. Cytokine signature profile may have a potential influence on the outcome of patients treated with bortezomib.

Multicentric Carpo-Tarsal Osteolysis Syndrome Mimicking Juvenile Idiopathic Arthritis: Two Case Reports and Review of the Literature

Multicentric carpo-tarsal osteolysis syndrome (MCTO) is a rare skeletal disorder commonly caused by MAF bZIP transcription factor B (MAFB) mutation. Clinically, it is characterized by aggressive osteolysis, which mainly affects the carpal tarsal bones, and is frequently associated with progressive nephropathy. Since the painful swelling and motion limitation on the wrists and/or ankles of MCTO mimics those of juvenile idiopathic arthritis (JIA), very often, MCTO is misdiagnosed as JIA. Here, we report two MCTO patients initially diagnosed with JIA but showed no response to treatment: P1, with a medical history of more than 10 years, was presented with a typical triad of arthritis-osteolysis-nephropathy; while P2 showed oligoarthritis. Gene tests were then taken and revealed a novel mutation, p.P63Q, and a previously reported conversion, p.S54L, in the MAFB gene. We also summarized the clinical and genetic features of a cohort containing 49 genetically confirmed MCTO patients. All 51 gene-confirmed MCTO cases (49 identified from the literature plus two patients identified herein) developed the disease during childhood. The median delay in diagnosis was 3.83 years (0–35 years). All cases presented bony lesions, and two-thirds had secondary renal lesions (32/48; three unknown), half of which (16/32) progressed into renal failure. Almost two-thirds (34/51), 75% (38/51), and 71% (36/51) of patients had no record of eye problems, facial abnormalities, and other manifestations. Most were misdiagnosed as JIA but didn't respond to treatment. Based on our experience, we suggest that clinicians should comprehensively evaluate the involvement of multiple systems in JIA patients, especially the kidney and eyes. And for JIA patients who underwent more than 3-month treatment with Bio-DMARD, genetic tests are recommended when they show little/no clinical and imaging changes, their high disease activity remains, and their disease activity remission is <50%, especially when combined with a triad of arthritis-osteolysis-nephropathy.

The Role of High Resolution Ultrasound In Comparison To MRI In The Evaluation Of Painful Knee

Background The knee joint is one of the most commonly injured joints in the body. Because of its complex structure, the joint is subjected to numerous pathologies and due to the recent increase in various sport activities; there has been a parallel increase in sport-induced internal derangements of the knee. Ultrasound is emerging as a viable imaging modality in the assessment of the musculoskeletal system lesions especially in experienced hands Objective To evaluate the role of high resolution dynamic ultrasonography as a diagnostic tool in the assessment of different causes of knee joint pain compared to MR imaging. Patients and Methods This study included 50 patients with painful knee joints as 32 females and 18 males, 16 patients had bilateral knee examination. Their ages ranged between 5-66 years. The cases was referred to a private radiological center, some of them referred to assess the knee joint pain by ultrasound as a fast and cheapest modality, yet most of the cases referred to evaluate the knee joint by MRI and the ultrasound was done as complementary study. Results Comparing between ultrasound and MRI in evaluation of painful knee joints, although the ultrasound has role in evaluation of bursal, synovial and peri-articular soft tissue lesions, the MRI is advised as a primary imaging tool for cruciates, meniscal and ligamentous lesions when clinically suspected. Conclusion Ultrasonography is a safe, cheap and efficient tool in the evaluation of the peri articular soft tissues with limited screening role at the internal knee joint cruciate / meniscal derangements as well as some bony lesions involving the bony cortex. It has no role in the intramedullary bony lesions. At this point, we concluded that ultrasonography has an important complementary role with MRI examination in the evaluation of the knee pain of different causes yet it is operator dependent and needs experience.

Fashioning Osteochondral Allograft for Humeral Head Defects in Reverse Hill-Sachs Lesions – A Proposed Surgical Technique

Introduction:Posterior glenohumeral joint dislocations with associated bony lesions are challenging to treat; namely, reverse Hill-Sachs’s lesions increase humeral head excursion predisposing to recurrent dislocations. To add to the complexity of management, posterior shoulder dislocations are often missed on plain radiographs, leading to chronicity in presentation. Case Report:We describe here our technique in our case series of three patients. Case I, 32 years, gentleman, presented 3 days after injury. He had a locked posterior dislocation of shoulder which he sustained while he fell asleep and hit a glass table. Shoulder was not reducible in emergency department. Reverse Hill- Sachs’s lesion involved 40% of humeral head. Case II, a 54- years- old gentleman, a keen gym trainer . Following sudden withdrawal of diazepam, he woke up lying on the floor and started experiencing shoulder pain. He presented a week following the injury. The dislocated shoulder could not be reduced in emergency department. Bony defect involved 50% of humeral head. Case III, 45 years gentleman who fell off from bike, presented on the same day to the emergency department. The dislocated shoulder was reduced. Defect size was 40% of humeral head. A thorough physical and radiological examination was performed to evaluate the lesion. Delto-pectoral approach was utilized for surgical exposure. Once fully assessed, the lesion is outlined and an oscillating saw is used to create uniform edges - – a regular “orange slice”- shaped defect. The prepared defect size is measured. Calcium phosphate cement is used to fill the defect and form a mould that represents the dimensions of allograft required to recreate the native sphericity of the humeral head. This mould then acts as a reference when fashioning the osteochondral femoral allograft to make sure this fits the defect anatomically. Once the graft is prepared, it is placed into the defect in the correct orientation and fixed in situ using headless s

Osteonecrosis as the presenting feature in a child with acute lymphoblastic leukaemia

A seven-year-old girl presented with pain in multiple joints and constitutional symptoms over a period of four months. There were no significant clinical findings apart from joint tenderness. Blood test results did not indicate any specific pathology and initial radiology imaging was normal. Subsequent careful examination of her X-ray images led to an MRI of her left knee, which revealed acute osteonecrotic changes. A following whole-body MRI examination demonstrated multifocal bony lesions. Bone marrow examination conclusively diagnosed acute lymphoblastic leukaemia (ALL). Acute osteonecrosis has classically been described as a complication of treatment in children with ALL and has not been recognised as a presenting feature until recently.